Proteínas oxidadas de origen animal y su impacto sobre la salud intestinal / Oxidized proteins of animal origin and their impact on intestinal health / Proteínas oxidadas de origem animal e seu impacto na saúde intestinal

Los alimentos de origen animal como la carne de pollo, res, pescado y cerdo poseen una amplia demanda en todo el mundo debido, entre otros aspectos, a su valor nutricional, asociado al alto contenido proteico. No obstante, este tipo de proteínas son susceptibles de sufrir reacciones de oxidación, las cuales pueden mediar procesos de fragmentación, agregación, pérdida de solubilidad, funcionalidad y digestibilidad proteica; eventos implicados en la pérdida de su valor nutricional. En este sentido, las proteínas agrega­das tienden a no ser digeridas en el tracto gastrointestinal y acumularse en el intestino (colon), donde la microbiota colónica las degrada a productos mutagénicos como fenol y p-cresol, lo que incrementa el riesgo de cáncer colorrectal. Por otra parte, los ami­noácidos o péptidos oxidados liberados en la digestión podrían incorporarse en las vías de señalización celular intestinal y favorecer o exacerbar procesos intestinales crónicos como colon irritable o enfermedad de Crohn. Debido al gran interés de esta temática en los últimos años, el objetivo de esta revisión es realizar una descripción general del impacto de proteínas oxidadas de origen animal sobre la salud intestinal.

Animal foods such as chicken, beef, fish and pork are in wide demand throughout the world due, among other things, to their nutritional value, associated with their high protein content. However, this type of protein is susceptible to oxidation reactions, which can mediate processes of fragmentation, aggregation, loss of solubility, functionality, and protein digestibility, which are events involved in the loss of their nutritional value. In this sense, aggregated proteins tend not to be digested in the gastrointestinal tract and accumulate in the intestine (colon), where the colonic microbiota degrades them into mutagenic products such as phenol and p-cresol, which increases the risk of colorectal cancer. On the other hand, the oxidized amino acids or peptides released in digestion could be incorporated into intestinal cell signaling pathways and favor or exacerbate chronic intestinal processes such as irritable bowel syndrome or Crohn's disease. Due to the great interest in this topic in recent years, the objective of this review is to provide a general overview of the impact of oxidized proteins of animal origin on intestinal health.

Alimentos de origem animal como frango, carne bovina, peixe e carne suína são muito procurados em todo o mundo devido, entre outros fatores, ao seu valor nutricional, associado ao seu alto teor de proteínas. No entanto, esse tipo de proteína é suscetível a reações de oxidação, que podem mediar processos de fragmentação, agregação, perda de solubilidade, funcionalidade e digestibilidade da proteína; eventos envolvidos na perda de seu valor nutritivo. Nesse sentido, as proteínas agregadas tendem a não ser digeridas no trato gastrointestinal e se acumulam no intestino (cólon), onde a microbiota colônica as degrada em produtos mutagênicos como fenol e p - cresol, aumentando o risco de câncer colorretal. Por outro lado, os aminoácidos ou peptídeos oxidados liberados na digestão poderiam ser incorporados às vias de sinalização das células intestinais e favorecer ou exacerbar processos intestinais crônicos, como a síndrome do intestino irritável ou a doença de Crohn. Devido ao grande interesse neste tema nos últimos anos, o objetivo desta revisão é fornecer uma descrição geral do impacto das proteínas oxidadas de origem animal na saúde intestinal.

Zinc delivery system constructed from food-borne nanoparticles derived from Undaria pinnatifida.

Food-borne nanoparticles from Undaria pinnatifida (UPFNs) were prepared and successfully applied as nanocarriers for microelement zinc delivery. UPFNs were spherical nanoparticles with average sizes of about 4.07 ± 1.09 nm, which chelated with zinc ions through amino nitrogen and carboxyl oxygen atoms as characterized by X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance spectroscopy. Thermodynamic analysis revealed that the overall chelation process between UPFNs and zinc ions was a spontaneous enthalpy-driven endothermic reaction. Compared to zinc sulfate, UPFN-Zn2+ showed higher solubility both in phytic acid solution and the process of gastrointestinal digestion. Meanwhile, no obvious cytotoxicity was found in UPFNs and UPFN-Zn2+. Specifically, UPFN-Zn2+ could successfully rescue cell viability, DNA replication activity and restore cell proliferation ability in zinc-deficient cells induced by a specific zinc chelator TPEN. Overall, UPFNs might serve as efficient, stable, and safe nanocarriers for zinc delivery.

3,3'-Diindolylmethane Suppresses the Growth of Hepatocellular Carcinoma by Regulating Its Invasion, Migration, and ER Stress-Mediated Mitochondrial Apoptosis.

Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death worldwide with limited treatment options. Biomarker-based active phenolic flavonoids isolated from medicinal plants might shed some light on potential therapeutics for treating HCC. 3,3'-diindolylmethane (DIM) is a unique biologically active dimer of indole-3-carbinol (I3C), a phytochemical compound derived from Brassica species of cruciferous vegetables-such as broccoli, kale, cabbage, and cauliflower. It has anti-cancer effects on various cancers such as breast cancer, prostate cancer, endometrial cancer, and colon cancer. However, the molecular mechanism of DIM involved in reducing cancer risk and/or enhancing therapy remains unknown. The aim of the present study was to evaluate anti-cancer and therapeutic effects of DIM in human hepatoma cell lines Hep3B and HuhCell proliferation was measured with MTT and trypan blue colony formation assays. Migration, invasion, and apoptosis were measured with Transwell assays and flow cytometry analyses. Reactive oxygen species (ROS) intensity and the loss in mitochondrial membrane potential of Hep3B and Huh7 cells were determined using dihydroethidium (DHE) staining and tetramethylrhodamine ethyl ester dye. Results showed that DIM significantly suppressed HCC cell growth, proliferation, migration, and invasion in a concentration-dependent manner. Furthermore, DIM treatment activated caspase-dependent apoptotic pathway and suppressed epithelial-mesenchymal transition (EMT) via ER stress and unfolded protein response (UPR). Taken together, our results suggest that DIM is a potential anticancer drug for HCC therapy by targeting ER-stress/UPR.

Aquaculture Production of the Brown Seaweeds Laminaria digitata and Macrocystis pyrifera: Applications in Food and Pharmaceuticals.

Seaweeds have a long history of use as food, as flavouring agents, and find use in traditional folk medicine. Seaweed products range from food, feed, and dietary supplements to pharmaceuticals, and from bioenergy intermediates to materials. At present, 98% of the seaweed required by the seaweed industry is provided by five genera and only ten species. The two brown kelp seaweeds Laminaria digitata, a native Irish species, and Macrocystis pyrifera, a native New Zealand species, are not included in these eleven species, although they have been used as dietary supplements and as animal and fish feed. The properties associated with the polysaccharides and proteins from these two species have resulted in increased interest in them, enabling their use as functional foods. Improvements and optimisations in aquaculture methods and bioproduct extractions are essential to realise the commercial potential of these seaweeds. Recent advances in optimising these processes are outlined in this review, as well as potential future applications of L. digitata and, to a greater extent, M. pyrifera which, to date, has been predominately only wild-harvested. These include bio-refinery processing to produce ingredients for nutricosmetics, functional foods, cosmeceuticals, and bioplastics. Areas that currently limit the commercial potential of these two species are highlighted.

From Fish Waste to Value: An Overview of the Sustainable Recovery of Omega-3 for Food Supplements.

The disposal of food waste is a current and pressing issue, urging novel solutions to implement sustainable waste management practices. Fish leftovers and their processing byproducts represent a significant portion of the original fish, and their disposal has a high environmental and economic impact. The utilization of waste as raw materials for the production of different classes of biofuels and high-value chemicals, a concept known as "biorefinery", is gaining interest in a vision of circular economy and zero waste policies. In this context, an interesting route of valorization is the extraction of omega-3 fatty acids (ω-3 FAs) for nutraceutical application. These fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have received attention over the last decades due to their beneficial effects on human health. Their sustainable production is a key process for matching the increased market demand while reducing the pressure on marine ecosystems and lowering the impact of waste production. The high resale value of the products makes this waste a powerful tool that simultaneously protects the environment and benefits the global economy. This review aims to provide a complete overview of the sustainable exploitation of fish waste to recover ω-3 FAs for food supplement applications, covering composition, storage, and processing of the raw material.

A Review of Hemp as Food and Nutritional Supplement.

The term "hemp" refers to Cannabis sativa cultivars grown for industrial purposes that are characterized by lower levels of tetrahydrocannabinol (THC), the active principle responsible for Cannabis psychotropic effects. Hemp is an extraordinary crop, with enormous social and economic value, since it can be used to produce food, textiles, clothing, biodegradable plastics, paper, paint, biofuel, and animal feed, as well as lighting oil. Various parts of the hemp plant represent a valuable source of food and ingredients for nutritional supplements. While hemp inflorescence is rich in nonpsychoactive, yet biologically active cannabinoids, such as cannabidiol (CBD), which exerts potent anxiolytic, spasmolytic, as well as anticonvulsant effects, hempseed has a pleasant nutty taste and represents a valuable source of essential amino acids and fatty acids, minerals, vitamins, and fibers. In addition, hempseed oil is a source of healthy polyunsaturated fatty acids, and hemp sprouts are rich in antioxidants. This review article aims to provide a comprehensive outlook from a multidisciplinary perspective on the scientific evidence supporting hemp beneficial properties when consumed as food or supplement. Marketing of hemp-derived products is subjected to diversified and complex regulations worldwide for several reasons, including the fact that CBD is also the active principal of pharmaceutical agents and that regulatory bodies in some cases ban Cannabis inflorescence regardless of its THC content. Some key regulatory aspects of such a complex scenario are also analyzed and discussed in this review article.

Nutritional Orthopedics and Space Nutrition as Two Sides of the Same Coin: A Scoping Review.

Since the Moon landing, nutritional research has been charged with the task of guaranteeing human health in space. In addition, nutrition applied to Orthopedics has developed in recent years, driven by the need to improve the efficiency of the treatment path by enhancing the recovery after surgery. As a result, nutritional sciences have specialized into two distinct fields of research: Nutritional Orthopedics and Space Nutrition. The former primarily deals with the nutritional requirements of old patients in hospitals, whereas the latter focuses on the varied food challenges of space travelers heading to deep space. Although they may seem disconnected, they both investigate similar nutritional issues. This scoping review shows what these two disciplines have in common, highlighting the mutual features between (1) pre-operative vs. pre-launch nutritional programs, (2) hospital-based vs. space station nutritional issues, and (3) post-discharge vs. deep space nutritional resilience. PubMed and Google Scholar were used to collect documents published from 1950 to 2020, from which 44 references were selected on Nutritional Orthopedics and 44 on Space Nutrition. Both the orthopedic patient and the astronaut were found to suffer from food insecurity, malnutrition, musculoskeletal involution, flavor/pleasure issues, fluid shifts, metabolic stresses, and isolation/confinement. Both fields of research aid the planning of demand-driven food systems and advanced nutritional approaches, like tailored diets with nutrients of interest (e.g., vitamin D and calcium). The nutritional features of orthopedic patients on Earth and of astronauts in space are undeniably related. Consequently, it is important to initiate close collaborations between orthopedic nutritionists and space experts, with the musculoskeletal-related dedications playing as common fuel.

O uso terapêutico dos alimentos em meados do século XIX / The therapeutic use of food in the mid-19th century

Introdução: No decorrer do século XIX surgiram as primeiras informações a respeito das substâncias químicas contidas nos alimentos. A partir dessas descobertas, a higiene alimentar como meio terapêutico estabeleceu critérios para a prescrição de azote (nitrogênio) e carbone (carbono), bem como recomendações alimentares nos diferentes ciclos de vida e estados de convalescença. Objetivos: Este trabalhou buscou analisar como e para que fins eram prescritos alguns alimentos cuja composição química era caracterizada pela presença do azote (nitrogênio) e carbone (carbono). Método: Foram utilizados como fonte de pesquisa os cadernos de visitas (prontuários) de embarcações encontrados no Arquivo Histórico da Marinha Portuguesa, os tratados médicos do período e publicações referentes à história da ciência e nutrição. Resultados e discussão: Nos cadernos de visitas consultados (anos 1859 e1863), as refeições à base de alimentos de origem animal (ricos em azote), como os caldos de carne e de galinha, foram as mais prescritas aos doentes, pois se pautavam nos princípios da dieta fibrinosa, que promovia a reparação tecidual e crescimento da matéria orgânica. Considerações finais: Ao longo dos dois últimos séculos, muitas teorias a respeito da função dos alimentos se modificaram, mas parte significativa de seus pressupostos foram constituídos no decorrer do século XIX.

Introduction: During the 19th century, emerged the first information about the chemical substances contained in food. From these discoveries, food hygiene as a therapeutic mean established criteria for the prescription of nitrogen (nitrogen) and carbon (carbon), as well as dietary recommendations in the different life cycles and convalescent states. Objectives: This work sought to analyze how and for what purposes some foods whose chemical composition was characterized by the presence of nitrogen (nitrogen) and carbon (carbon)were prescribed . Methodology: The visiting notebooks (medical records) of vessels found in the Historical Archive of the Portuguese Navy, medical treaties of the period and publications referring to the history of science and nutrition were used as a research source. Results and discussion: In the consulted notebooks (years 1859 and 1863), meals based on animal foods (rich in nitrogen), such as meat and chicken broths, were the most prescribed to patients, as they were based on principles of the fibrinous diet, which promoted tissue repair and growth of organic matter. Final considerations: Over the past two centuries, many theories about the function of food have changed, but a significant part of their assumptions were made during the 19th century.

Dietary Contributors to Food Group Intake in Preschool Children Attending Family Childcare Homes: Differences between Latino and Non-Latino Providers.

While there are several factors that contribute to the diet quality of children in childcare, one contributing factor in Family Childcare Homes (FCCHs) is the provider's ethnicity. However, research examining the food items provided in this setting is limited; in particular, with regards to differences between FCCHs of Latino and non-Latino providers. The aim of this study was to identify and describe the food items that contribute to food group intake in preschool-aged children attending FCCHs, and to examine differences by provider ethnicity. This secondary data analysis used baseline data from Healthy Start/Comienzos Sanos: a cluster-randomized trial. Children's dietary intake was collected using the Dietary Observation in Child Care method and entered into Nutrition Data System for Research software. Food groups were based on the Nutrition Coordinating Center classification. Contribution of food items to their respective food group was calculated as a proportion, using ratio of means and presented as a percentage. Ethnic differences were tested with ANCOVA (p < 0.05) with Bonferroni adjustments for multiple comparisons. All providers (n = 120) were female and 67.5% were Latino. Most fruit consumed by children was in the form of juice (85%), three-fourths of the grains consumed were refined (75%), and half of the sweets consumed were syrup/honey/jelly (50%). Most of the vegetables consumed were non-starchy (61%), nearly three-fourths of dairy consumed was low-fat (71%), and vegetable oils contributed the most to the fats group (89%). Food items differed by provider's ethnicity, with children cared for by non-Latino providers consuming a higher proportion of fruit juice, animal fats and a lower proportion of legumes (p < 0.001 for all). Children with Latino providers consumed a lower proportion of non-starchy vegetables, low-fat dairy, and nuts/seeds (p < 0.001 for all). FCCH providers could offer more whole fruits and grains and a greater variety of vegetables. Differences by ethnicity suggest providers could benefit from culturally tailored recommendations.

Broccoli byproducts for protection and co-delivery of EGCG and tuna oil.

Neat epigallocatechin gallate (EGCG) has low bioavailability and tuna oil (TO) is prone to oxidation. Broccoli byproducts (BBP) were used for preparing TO-BBP (25% oil, dry basis) and TO-EGCG-BBP (20% oil and 20% EGCG, dry basis) powders. The gross composition and surface fat of powders and morphology of reconstituted emulsions were characterized. Oxipres® data (80 °C, 5 bar oxygen pressure) showed that the TO-EGCG-BBP formulation was more oxidatively stable [Induction period (IP) > 100 h] than TO-BBP (IP ~ 20 h). During in vitro digestion, 90% of EGCG was recovered in the whole intestinal digesta of the TO-EGCG-BBP formulation compared to 76% for the EGCG-BBP formulation and 66% for the neat EGCG. The use of BBP for co-delivering EGCG and TO increases oxidative stability of TO and improves EGCG stability during in vitro digestion. This study highlights the potential for formulating functional ingredient with BBP and contribute to food waste reduction.

Pseudocereal grains: Nutritional value, health benefits and current applications for the development of gluten-free foods.

Nowadays, consumers are more conscious of the environmental and nutritional benefits of foods. Pseudocereals grains, edible seeds belonging to dicotyledonous plant species, are becoming a current trend in human diets as gluten-free (GF) grains with excellent nutritional and nutraceutical value. Pseudocereals are a good source of starch, fiber, proteins, minerals, vitamins, and phytochemicals such as saponins, polyphenols, phytosterols, phytosteroids, and betalains with potential health benefits. The present review aims to summarize the nutritional quality and phytochemical profile of the three main pseudocereal grains: quinoa, amaranth and buckwheat. In addition, current evidence about their health benefits in animal models and human studies is also provided in detail. Based on the accumulating research supporting the inclusion of pseudocereals grains in the diet of celiac persons, this review discusses the recent advances in their application for the development of new GF products. Future directions for a wider cultivation and commercial exploitation of these crops are also highlighted.

Toxoplasma gondii Oocyst Infectivity Assessed Using a Sporocyst-Based Cell Culture Assay Combined with Quantitative PCR for Environmental Applications.

Toxoplasma gondii is a ubiquitous foodborne protozoan that can infect humans at low dose and displays different prevalences among countries in the world. Ingestion of food or water contaminated with small amounts of T. gondii oocysts may result in human infection. However, there are no regulations for monitoring oocysts in food, mainly because of a lack of standardized methods to detect them. The objectives of this study were (i) to develop a reliable method, applicable in biomonitoring, for the rapid detection of infectious oocysts by cell culture of their sporocysts combined with quantitative PCR (sporocyst-CC-qPCR) and (ii) to adapt this method to blue and zebra mussels experimentally contaminated by oocysts with the objective to use these organisms as sentinels of aquatic environments. Combining mechanical treatment and bead beating leads to the release of 84% ± 14% of free sporocysts. The sporocyst-CC-qPCR detected fewer than ten infectious oocysts in water within 4 days (1 day of contact and 3 days of cell culture) compared to detection after 4 weeks by mouse bioassay. For both mussel matrices, oocysts were prepurified using a 30% Percoll gradient and treated with sodium hypochlorite before cell culture of their sporocysts. This assay was able to detect as few as ten infective oocysts. This sporocyst-based CC-qPCR appears to be a good alternative to mouse bioassay for monitoring infectious T. gondii oocysts directly in water and also using biological sentinel mussel species. This method offers a new perspective to assess the environmental risk for human health associated with this parasite.IMPORTANCE The ubiquitous protozoan Toxoplasma gondii is the subject of renewed interest due to the spread of oocysts in water and food causing endemic and epidemic outbreaks of toxoplasmosis in humans and animals worldwide. Displaying a sensitivity close to animal models, cell culture represents a real alternative to assess the infectivity of oocysts in water and in biological sentinel mussels. This method opens interesting perspectives for evaluating human exposure to infectious T. gondii oocysts in the environment, where oocyst amounts are considered to be very small.

Enhanced dissolution and oral bioavailbility of cinacalcet hydrochlorde nanocrystals with no food effect.

This study was aimed at improving oral bioavailbility and reducing the food effect of cinacalcet hydrochlorde (CINA), a poorly soluble drug for the treatment of chronic kidney disease, by preparing its nanocrystals (NCs) utilizing the precipitation-ultrasonication method. Based on the single factor method and Box-Behnken design, with the particle size and polydispersity index (PDI) as indexes, the optimal formulation was achieved. It was investigated that the particle size and PDI of the NCs prepared on the basis of optimal formulation were 244 ± 2 nm and 0.168 ± 0.001, respectively. The NCs were solidificated by lyophilization. Scanning electron microscopy, differential scanning calorimetry and x-ray powder diffraction were used to characterize the CINA-NCs, and there was no crystalline change during preparation and lyophilization. The CINA-NCs capsules prepared with 30% (w/v) MCC, 8% (w/v) CCNa and 2% (w/v) talcum powder by orthogonal experimental design presented an enhanced in vitro dissolution rate in four media compared with commercial tablets Sensipar® and raw material. The raw material, blank NCs and CINA-NCs were confirmed to be non-toxic to Caco-2 cells when the drug concentration was below 250 µg ml-1. In the in vivo pharmacokinetic study, the Cmax (the peak concentration of CINA in plasma) and AUC0-t (area under curve by trapezoidal area method) of the CINA-NCs capsules were approximately 1.90-fold and 1.64-fold greater than that of Sensipar® in the fasted state. Overall, this nanotechnology is a promising way to optimize the dosage form of CINA oral administration.

Relação ancestral e pan-resistoma plasmidial de Escherichia coli produtora de CTX-M-8 e MCR-1 na interface humana, animal e ambiental / Ancestral relationship and plasmid pan-resistome of CTX-M-8- and MCR-1-producing Escherichia coli in human-animal-environmental interface

Linhagens de Escherichia coli produtoras de ß-lactamase de espectro estendido (ESßL) do tipo CTX-M são endêmicas no Brasil, sendo prevalentes em casos de infecções hospitalares e ambulatoriais. Atualmente, cepas produtoras de CTX-M têm sido recuperadas de ambientes urbanos, animais de companhia ou de produção e de alimentos de origem animal, inclusive afetando o agronegócio, o que aponta uma possível rota de disseminação em diferentes ecossistemas. Recentemente, nesta espécie, foi descoberto um novo gene, chamado de mcr-1, que confere resistência transferível à colistina, um dos últimos antibióticos eficazes para o tratamento de infecções causadas por bactérias produtoras de ESBL e carbapenemases. Deste modo, o presente estudo tem como objetivo elucidar os aspectos sobre a caracterização e a relação de plasmídeos que carregam genes do tipo blaCTX-M-8 e mcr- 1 em cepas de E. coli isoladas de seres humanos, animais, ambiente aquático e alimentos, no Brasil. Neste estudo são apresentados os resultados da análise plasmidial de 25 cepas de E. coli, das quais nove apresentaram o genótipo blaCTX-M-8/IncI1, 11 apresentaram o genótipo mcr-1/IncX4 e cinco apresentaram ambos os genótipos blaCTX-M-8/IncI1 e mcr-1/IncX4. Dos resultados, podemos observar que plasmídeos IncI1 (blaCTX-M-8) e IncX4 (mcr-1) estão circulando no Brasil desde o ano de 2009 entre diferentes clones (STs) de E. coli e em diferentes ambientes e hospedeiros. Os plasmídeos IncI1 foram conjugativos e pertencentes ao ST113, exceto o plasmídeo recuperado de um isolado humano, que foi pertencente ao ST131. Os plasmídeos IncI1 apresentaram sua arquitetura conservada, com a presença de genes de replicação, transferência e estabilidade. A partir do alinhamento, os plasmídeos IncI1 apresentaram 94-99% de similaridade genética entre eles. Dentre os plasmídeos IncX4, independente da fonte de isolamento, todos permaneceram com sua arquitetura altamente conservada. Entretanto, apenas dois plasmídeos (um encontrado em uma cepa de animal e outro encontrado em uma cepa de ambiente aquático) apresentaram uma IS1294, truncando o gene de mobilização. Na análise comparativa, todos os plasmídeos IncX4 apresentaram similaridade genética de 95-99,9% entre eles. No alinhamento de plasmídeos IncX4 brasileiros contra plasmídeos de outras regiões geográficas, foi observada similaridade genética > 99,9%, o que confirma a estabilidade e conservação desses plasmídeos. Neste estudo foram reportados dados inéditos da primeira identificação do gene mcr-1 em diferentes ecossistemas no Brasil, assim como a nova variante mcr-5.3. A análise filogenética dos plasmídeos IncI1 e IncX4, destacam que ambos compartilham uma arquitetura conservada, e a evolução é atribuída à aquisição de genes de resistência. Adicionalmente, um novo vetor de disseminação do gene mcr-1 no Brasil foi identificado - o plasmídeo IncHI2. Os resultados desse estudo demonstram o grave problema da resistência bacteriana dentro do conceito One-health e que, com o avanço de ferramentas moleculares, a identificação e a resolução desse problema poderá estar cada vez mais próxima de ser elucidada

CTX-M-type extended-spectrum-ß-lactamase (ESßL)-producing-Escherichia coli are endemic in Brazil and are prevalent in cases of nosocomial and ambulatory infections. Currently, CTXM-producing strains have been recovered from urban environments, companion/production animals and animal source foods, which indicates a possible route of dissemination in different ecosystems. Recently, in this species, a new gene, called mcr-1, has been discovered, conferring transferable resistance to colistin, one of the last effective antibiotics for the treatment of infections caused by ESBL- and carbapenemases -producing bacteria. Thus, the present study aims to elucidate unknown aspects of the pan-resistome and ancestral relationship of plasmids carrying blaCTX-M-8 and mcr-1 genes in strains of E. coli isolated from humans, animals, aquatic environment and food, in Brazil. In this study, we present results from the plasmidial analysis of 25 E. coli strains, from which nine presented the blaCTX-M-8/IncI1 genotype, 11 presented the mcr-1/IncX4, and five presented both blaCTX-M-8/IncI1 and mcr-1/IncX4 genotypes. Among these results, we can observe that IncI1 (blaCTX-M-8) and IncX4 (mcr-1) plasmids are circulating in Brazil since 2009, between different E. coli clones (STs) and different hosts and environments. IncI1 plasmids were conjugative and assigned to ST113, with exception of a plasmid recovered from a human isolate, which was assigned to ST131. IncI1 plasmids presented conserved architecture, with the presence of genes of replication, transference, and stability. From the alignment analysis, IncI1 plasmids presented 94-99% genetic similarity among them. Among the IncX4 plasmids, regardless the isolation source, their architecture remained highly conserved. However, only two plasmids (one detected in an animal's strain and another detected in an aquatic environment's strain) presented an IS1294, truncating the mobilization gene. In the comparative analysis, all IncX4 plasmids presented 95-99,9% genetic similarity among them. In the alignment of Brazilian IncX4 plasmids against plasmids from other geographic regions, >99.9% genetic similarity was observed, confirming the stability and conservation of these plasmids. In this study, unprecedented data from the first identification of the mcr-1 gene in different ecosystems in Brazil, as well as the new variant, mcr-5.3. Additionally, it was identified a new dissemination vector of the mcr-1 gene in Brazil - the IncHI2 plasmid. Phylogenetic analysis of IncI1and IncX4 plasmids highlight that both share a conserved backbone, and evolution is attributed to the acquisition of clinically relevant antimicrobial resistance genes. The results from this study demonstrate the serious problem of the bacterial resistance within the "One-Health" concept and that, with the advance of molecular tools, identification and resolution of this problem may be increasingly closer to being elucidate

New insight into organic anion transporters from the perspective of potentially important interactions and drugs toxicity.

The family of organic anion transporters (OATs) includes a group of over 10 transmembrane transporting proteins belonging to the solute carrier 22 subfamilies of the major facilitator superfamily. Their function is related to the transport of a great variety of organic anions against the electrical and chemical gradient. OATs are present in most types of human tissues, including the kidneys, liver, placenta, olfactory epithelium, retina, and choroid plexus tissues. The OATs family plays an important role in the cellular uptake, distribution, excretion, and detoxification of many water-soluble drugs, endogenous compounds, nutrition ingredients, environmental contaminants and toxins, and significantly impacts their efficacy, pharmacokinetics and toxicity, both in a preferable and unfavorable way. OATs demonstrated great potential to participate in many potentially relevant interactions, which may lead to unexpected, but not always detrimental, effects. Wider knowledge about their specific functions in the body, role in disease states, pharmacokinetics interactions, and intraindividual response to therapeutic treatment will allow to predict and prevent OAT-related adverse effects or use favorable interactions in pharmacotherapy, as well as to rationally design therapeutics targeted at individual transporter drugs with improved bioavailability, prolonged half-life or reduced toxicity, and improve safety guidelines concerning drug dosage. This review gathers recent reports regarding OAT-related essential interactions involving components of popular therapeutic herbal products, dietary supplements, and clinically important drugs, their significance and potential suitability in modulating the severity of drug-related side effects and toxicity mechanisms.

Improving effects of dietary rumen protected γ-aminobutyric acid additive on apparent nutrient digestibility, growth performance and health status in heat-stressed beef cattle.

This study was aimed to investigate the effects of rumen-protected γ-aminobutyric acid (RP-GABA) on apparent nutrient digestibility, growth performance and health status in heat stressed beef cattle. Fifty Jinjiang Yellow cattle were randomly assigned to 5 treatments (10 animals/treatment). Treatments 1 to 5 were basal diets affixed with 0 (control), 8, 16, 24 and 32 mg of RP-GABA/kg of body weight (BW) respectively. The trial lasted 45 days. Apparent digestibility of crude protein (CP), crude fiber (CF) and calcium (Ca) quadratically increased with increasing RP-GABA (p < .01), while apparent digestibility of phosphorus (P) tended to quadratically increase (p = .09). Dietary supplementation with increasing RP-GABA linearly increased DM digestibility and average daily gain (ADG) (p < .01), whereas the feed to gain (F:G) ratio linearly decreased with increasing RP-GABA (p < .01). The average daily feed intake (ADFI) value tended to linearly increase with RP-GABA supplementation (p = .08). Total protein (TP), blood urea nitrogen (BUN) and malondialdehyde (MDA) levels quadratically decreased (p < .01) with increasing RP-GABA, however albumin (ALB), glucose (GLU), superoxide dismutase (SOD), triiodothyronine (T3) and thyroxine (T4) levels quadratically increased (p ≤ .01). In conclusion, the present results indicated that dietary supplementation with RP-GABA led to improved nutrient digestibility, growth performance and antioxidant status in heat stressed beef cattle.

Steroid Hormone Vitamin D: Implications for Cardiovascular Disease.

Understanding of vitamin D physiology is important because about half of the population is being diagnosed with deficiency and treated with supplements. Clinical guidelines were developed based on observational studies showing an association between low serum levels and increased cardiovascular risk. However, new randomized controlled trials have failed to confirm any cardiovascular benefit from supplementation in the general population. A major concern is that excess vitamin D is known to cause calcific vasculopathy and valvulopathy in animal models. For decades, administration of vitamin D has been used in rodents as a reliable experimental model of vascular calcification. Technically, vitamin D is a misnomer. It is not a true vitamin because it can be synthesized endogenously through ultraviolet exposure of the skin. It is a steroid hormone that comes in 3 forms that are sequential metabolites produced by hydroxylases. As a fat-soluble hormone, the vitamin D-hormone metabolites must have special mechanisms for delivery in the aqueous bloodstream. Importantly, endogenously synthesized forms are carried by a binding protein, whereas dietary forms are carried within lipoprotein particles. This may result in distinct biodistributions for sunlight-derived versus supplement-derived vitamin D hormones. Because the cardiovascular effects of vitamin D hormones are not straightforward, both toxic and beneficial effects may result from current recommendations.

Bioaccessible selenium sourced from Se-rich mustard cake facilitates protection from TBHP induced cytotoxicity in melanoma cells.

Selenium (Se) is an essential dietary supplement that resolves inflammatory responses and offers antioxidant cytoprotection. In this study, we present the data on the cytoprotective effect of Se-rich mustard protein isolated from mustard cultivated in seleniferous soils in Punjab, India. The concentrations of total Se in mustard seed, oil-free mustard cake, and mustard protein were 110.0 ± 3.04, 143.0 ± 5.18, and 582.3 ± 6.23 µg g-1, respectively. The cytoprotective effect of Se-rich mustard protein was studied on tert-butyl hydroperoxide (TBHP)-induced cytotoxicity in a mouse melanoma cell line (B16-F10). When compared with TBHP treated cells (where no viable cells were found), Se-rich protein made bioaccessible through simulated gastrointestinal digestion protected melanoma cells from cytotoxicity with decreased levels of oxidative stress resulting in 73% cell viability. Such an effect was associated with a significant increase in glutathione peroxidase activity as a function of bioaccessible Se and its response towards cytoprotection.

Uso indiscriminado de pesticidas y ausencia de control sanitario para el mercado interno en Perú

[RESUMEN]. Notificar el nivel de contaminación de los alimentos de origen animal y vegetal monitorizados por la autoridad sanitaria en Perú, que realiza el Servicio Nacional de Sanidad Agraria (SENASA), para poder informar al consumidor y a las autoridades nacionales de la situación del control sanitario del mercado interno en el país. La información se ha obtenido de los informes incluidos en la página web del SENASA. Los datos considerados corresponden a los de los informes de evaluación de todos los tipos de alimentos de origen vegetal y animal analizados en el período comprendido entre 2011 y 2015. Para este período, los resultados muestran que 202 muestras de animales y vegetales incumplen las normas (son no conformes). El porcentaje de muestras de alimentos de origen animal no conformes fue 12,68% y el correspondiente a alimentos de origen vegetal, 24,87%. En el periodo estudiado, se observó un aumento de 30,73% de las muestras no conformes, que incluso ha alcanzado 50%. Los niveles de contaminación de los alimentos de origen animal y vegetal monitorizados por el SENASA son preocupantes. Por ello, se recomienda iniciar acciones concretas para afrontar esta situación, confiando en que estas acciones sean priorizadas y planificadas con la participación de todos los actores del sistema agrícola de Perú a fin de introducir los cambios regulatorios necesarios y establecer indicadores claros, medibles y alcanzables de monitorización y control para proteger la salud de la población.

[ABSTRACT]. This communication seeks to report the level of contamination of foodstuffs of animal and vegetable origin monitored by a health authority of Peru, namely the National Agrarian Health Service (SENASA), in order to inform consumers and national authorities of the current situation of sanitary control of the Peruvian domestic market. Information was obtained from reports posted on the SENASA website. The data considered correspond to those present in evaluation reports of all food types of vegetable and animal origin analyzed in the period 2011–2015. Results for this period show that 202 samples of animal and plant origin were in violation of standards (noncompliant). Overall, 12.68% of food samples of animal origin and 24.87% of food samples of vegetable origin were noncompliant. Over the course of the studied period, a 30.73% increase in the proportion of noncompliant samples was observed, reaching as high as 50%. The levels of contamination of foods of animal and vegetable origin monitored by SENASA are concerning. It is thus recommended that concrete actions be implemented to address this situation, and that these actions be prioritized and planned with the involvement of all actors in Peru’s agricultural system in order to introduce the necessary regulatory changes and establish clear, measurable, and achievable indicators of monitoring and control to protect the health of the population.

[RESUMO]. Notificar o grau de contaminação de alimentos de origem animal e vegetal medido pela agência sanitária do Peru (Serviço Nacional de Sanidade Agrária, SENASA) a fim de informar o consumidor e as autoridades nacionais da situação de controle sanitário do mercado interno do país. A informação foi obtida de informes publicados no website do SENASA. Os dados correspondem aos obtidos de informes de avaliação de todos os tipos de alimentos de origem animal e vegetal analisados no período entre 2011 e 2015. Os resultados obtidos para o período de estudo revelam que 202 amostras de alimentos de origem animal e vegetal descumprem as normas (não conformidade). O percentual de amostras não conformes foi 12,68% para os alimentos de origem animal e 24,87% para os alimentos de origem vegetal. Observou-se neste período aumento de 30,73% das amostras em não conformidade, inclusive alcançando 50%. O grau de contaminação dos alimentos de origem animal e vegetal medido pelo SENASA é preocupante. Recomendam-se medidas concretas para enfrentar este problema e tais medidas devem ser priorizadas e planejadas com a participação de todos os interessados diretos do sistema agrícola do Peru a fim de introduzir as mudanças reguladoras necessárias e estabelecer indicadores claros, mensuráveis e alcançáveis para monitoramento e controle para proteger a saúde da população.